The goal of the parent grant (R01HD092419; PI: Dr. Joseph Costello) is to characterize the transcriptomic and epigenomic alterations in human placental cytotrophoblasts (CTBs) that occur in severe preeclampsia (sPE). We propose extending these analyses to CTBs isolated from placentas collected from pregnancies affected by Down Syndrome (DS) or trisomy 21 (T21). These experiments build on our finding that the maternal-fetal interface in DS has defects (e.g., impaired CTB differentiation, shallow placentation) that are similar to those observed in sPE. Thus, we propose testing the hypothesis that the similarities in the epigenetic regulators of the CTB phenotype in the two conditions will give us added insights into common mechanistic drivers. Differences could explain why relatively few women carrying T21 fetuses develop sPE (2), and shed light on placental factors that could be drivers of the wide variations observed in the DS phenotype.